This application requests state-of-the-art components essential for 1) establishing biological solid-state NMR at UCSF;and 2) considerably enhancing current efforts focused on investigating metabolic pathways and biomarkers for human diseases. The needed instrument is a combined liquids and solid-state 600 MHz NMR spectrometer console and accessories that allow: 1) High-resolution triple-resonance magic-angle spinning experiments to perform conformational analyses of mammalian and fungal prion protein fibrils;2) high-throughput, automated, multinuclear detection of cell extracts to establish correlations with NMR detectable biomarkers;and 3) development of new, ultra-sensitive NMR techniques to monitor ligand binding to macromolecules using Dynamic Nuclear Polarization. Each of these areas are heavily supported at the University of California by the NIH, with investigations spanning from basic to translational science. The new instrument will have a broad impact on human health by providing insight into molecular bases for neurodegenerative disease, diagnostic treatments for cancer, and new tools for drug discovery.